Project Abstract Cervical cancer is a leading cause of cancer-related mortality among women in low- and middle-income countries (LMICs). The World Health Organization recently released guidelines that endorse alternatives to cytology-based screening, including HPV-based screening and visual inspection with acetic acid (VIA), which will facilitate increased screening coverage and detection of curable precursors to cervical cancer. In order to reduce the burden of cervical cancer, highly effective screening strategies must be combined with affordable and accessible treatment of precancerous lesions. The standard treatment for cervical precancer, gas-based cryotherapy, is often not accessible in LMICs because gas tanks are generally expensive, difficult to obtain, and hard to transport. With the number of screening options increasing, an urgent need exists for a point-of- care treatment technology that is accessible, portable, and inexpensive. We innovated the original thermoablator, an existing cervical precancer treatment device with a probe heated to 100-120 C, for use on a wider scale by customizing the device for LMICs in order to meet this need. This academic-industrial partnership will compare this novel device to traditional CO2-based cryotherapy for the treatment of cervical precancer in LMICs. The Specific Aims of this project are to 1) modify a novel thermoablation prototype adapted and optimized specifically for treatment of cervical precancer in LMICs, determine a more nearly optimal patient- centered protocol for treatment of high-grade precancer, demonstrate that the efficacy of LMIC-adapted thermoablator is non-inferior to CO2-based cryotherapy for the treatment of cervical precancer, and determine the cost-effectiveness of all evaluated therapeutic and post-treatment surveillance strategies. The hypothesis being tested is that this novel device is non-inferior to CO2-based cryotherapy in terms of clinical validity and cost- effectiveness. The research team has well-established relationships with leading regional organizations that provide guidance to government-run cervical cancer prevention programs. Deployment of the LMIC-adapted thermoablator to existing programs will not only improve program efficacy, but will also serve as a model for adoption of this technology in the region. The results of this study will affect other research areas by serving as a springboard to exploring treatment alternatives that are amenable to low-resource settings and thus will reach the most vulnerable populations.